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Science Advances May 2022Endogenous viral elements (EVEs), accounting for 15% of our genome, serve as a genetic reservoir from which new genes can emerge. Nematode EVEs are particularly diverse...
Endogenous viral elements (EVEs), accounting for 15% of our genome, serve as a genetic reservoir from which new genes can emerge. Nematode EVEs are particularly diverse and informative of virus evolution. We identify Atlas virus-an intact retrovirus-like EVE in the human hookworm , with an envelope protein genetically related to G-G glycoproteins from the family Phenuiviridae. A cryo-EM structure of Atlas G reveals a class II viral membrane fusion protein fold not previously seen in retroviruses. Atlas G has the structural hallmarks of an active fusogen. Atlas G trimers insert into membranes with endosomal lipid compositions and low pH. When expressed on the plasma membrane, Atlas G has cell-cell fusion activity. With its preserved biological activities, Atlas G has the potential to acquire a cellular function. Our work reveals structural plasticity in reverse-transcribing RNA viruses.
Topics: Ancylostomatoidea; Animals; Humans; Phlebovirus; RNA Viruses; Viral Envelope Proteins; Viral Fusion Proteins; Virus Internalization
PubMed: 35544562
DOI: 10.1126/sciadv.abj6894 -
Proceedings of the National Academy of... Sep 2017Severe fever with thrombocytopenia syndrome virus (SFTSV) and Rift Valley fever virus (RVFV) are two arthropod-borne phleboviruses in the family, which cause severe...
Severe fever with thrombocytopenia syndrome virus (SFTSV) and Rift Valley fever virus (RVFV) are two arthropod-borne phleboviruses in the family, which cause severe illness in humans and animals. Glycoprotein N (Gn) is one of the envelope proteins on the virus surface and is a major antigenic component. Despite its importance for virus entry and fusion, the molecular features of the phleboviruse Gn were unknown. Here, we present the crystal structures of the Gn head domain from both SFTSV and RVFV, which display a similar compact triangular shape overall, while the three subdomains (domains I, II, and III) making up the Gn head display different arrangements. Ten cysteines in the Gn stem region are conserved among phleboviruses, four of which are responsible for Gn dimerization, as revealed in this study, and they are highly conserved for all members in Therefore, we propose an anchoring mode on the viral surface. The complex structure of the SFTSV Gn head and human neutralizing antibody MAb 4-5 reveals that helices α6 in subdomain III is the key component for neutralization. Importantly, the structure indicates that domain III is an ideal region recognized by specific neutralizing antibodies, while domain II is probably recognized by broadly neutralizing antibodies. Collectively, Gn is a desirable vaccine target, and our data provide a molecular basis for the rational design of vaccines against the diseases caused by phleboviruses and a model for bunyavirus Gn embedding on the viral surface.
Topics: Animals; Antibodies, Neutralizing; Bunyaviridae Infections; Cell Line; Crystallography, X-Ray; Epitopes; Glycoproteins; Phlebovirus; Rift Valley Fever; Rift Valley fever virus; Sf9 Cells; Viral Envelope Proteins; Virus Internalization
PubMed: 28827346
DOI: 10.1073/pnas.1705176114 -
PLoS Neglected Tropical Diseases Aug 2021With global warming and lush forest change, vector-borne infections are expected to increase in the number and diversity of agents. Since the first report of severe...
With global warming and lush forest change, vector-borne infections are expected to increase in the number and diversity of agents. Since the first report of severe fever with thrombocytopenia syndrome (SFTS) in 2013, the number of reported cases has increased annually in South Korea. However, although tick-borne encephalitis virus (TBEV) was detected from ticks and wild rodents, there is no human TBE case report in South Korea. This study aimed to determine the seroprevalence of TBEV and SFTS virus (SFTSV) among forest and field workers in South Korea. From January 2017 to August 2018, a total 583 sera were obtained from the forest and field workers in South Korea. IgG enzyme-linked immunosorbent assay (ELISA) and neutralization assay were conducted for TBEV, and indirect immunofluorescence assay (IFA) and neutralization assay were performed for SFTSV. Seroprevalence of TBEV was 0.9% (5/583) by IgG ELISA, and 0.3% (2/583) by neutralization assay. Neutralizing antibody against TBEV was detected in a forest worker in Jeju (1:113) and Hongcheon (1:10). Only 1 (0.2%) forest worker in Yeongju was seropositive for SFTSV by IFA (1:2,048) and neutralizing antibody was detected also. In conclusion, this study shows that it is necessary to raise the awareness of physicians about TBEV infection and to make efforts to survey and diagnose vector-borne diseases in South Korea.
Topics: Adult; Aged; Aged, 80 and over; Antibodies, Neutralizing; Antibodies, Viral; Encephalitis Viruses, Tick-Borne; Encephalitis, Tick-Borne; Female; Forestry; Humans; Male; Middle Aged; Phlebovirus; Republic of Korea; Seroepidemiologic Studies; Severe Fever with Thrombocytopenia Syndrome; Vector Borne Diseases; Young Adult
PubMed: 34407077
DOI: 10.1371/journal.pntd.0009687 -
Viruses Apr 2021We report the isolation of a newly recognized phlebovirus, Hedi virus (HEDV), from sandflies collected in Shanxi Province, China. The virus' RNA is comprised of three...
We report the isolation of a newly recognized phlebovirus, Hedi virus (HEDV), from sandflies collected in Shanxi Province, China. The virus' RNA is comprised of three segments. The greatest amino acid sequence similarity of the three gene segments between this virus and previously recognized phleboviruses is 40.85-63.52%, and the RNA-dependent RNA polymerase (RdRp) amino acid sequence has the greatest similarity (63.52%) to the Rift Valley fever virus (RVFV) ZH-548 strain. Phylogenetic analysis of the amino acid sequence of the virus RdRp indicated that HEDV is close to RVFV and distinct from other phleboviruses, forming its own evolutionary branch. We conclude that it is necessary to increase the monitoring of phleboviruses carried by sandflies in China.
Topics: Animals; China; Genome, Viral; Genomics; Phlebotomus Fever; Phlebovirus; Phylogeny; Psychodidae; RNA, Viral; Virus Replication; Whole Genome Sequencing
PubMed: 33925561
DOI: 10.3390/v13050772 -
Viruses May 2021Viral non-structural proteins, such as NSs of the newly emerging severe fever with thrombocytopenia syndrome virus, are well established virulence factors, mediating... (Review)
Review
Viral non-structural proteins, such as NSs of the newly emerging severe fever with thrombocytopenia syndrome virus, are well established virulence factors, mediating viral pathogenesis and disease progression through various mechanisms. NSs has been described as a potent interferon antagonist and NF-κB agonist, two divergent signaling pathways in many immune responses upon a viral encounter. In this review, we highlight the many mechanisms used by NSs on the host that promote viral replication and hyper-inflammation. Understanding these host-pathogen interactions is crucial for antiviral therapy development.
Topics: Animals; Biomarkers; Cytokine Release Syndrome; Cytokines; Disease Models, Animal; Disease Susceptibility; Host-Pathogen Interactions; Humans; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome; Viral Nonstructural Proteins; Virus Replication
PubMed: 34064604
DOI: 10.3390/v13050876 -
Antiviral Research Jan 2021Severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland virus (HRTV) cause viral hemorrhagic fever-like illnesses in humans due to an aberrant host...
Severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland virus (HRTV) cause viral hemorrhagic fever-like illnesses in humans due to an aberrant host inflammatory response, which contributes to pathogenesis. Here, we established two separate minigenome (MG) systems based on the M-segment of SFTSV and HRTV. Following characterization of both systems for SFTSV and HRTV, we used them as a platform to screen potential compounds that inhibit viral RNA synthesis. We demonstrated that the NF-κB inhibitor, SC75741, reduces viral RNA synthesis of SFTSV and HRTV using our MG platform and validated these results using infectious SFTSV and HRTV. These results may lead to the use of MG systems as potential screening systems for the identification of antiviral compounds and yield novel insights into host-factors that could play role in bandavirus transcription and replication.
Topics: Animals; Antiviral Agents; Chlorocebus aethiops; Drug Discovery; Genome, Viral; HEK293 Cells; Host-Pathogen Interactions; Humans; Inhibitory Concentration 50; NF-kappa B; Phlebovirus; THP-1 Cells; Ticks; Vero Cells
PubMed: 33296695
DOI: 10.1016/j.antiviral.2020.104993 -
Viruses Nov 2023Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infection caused by the SFTS virus (SFTSV), with a high fatality rate of approximately 30% in humans....
Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infection caused by the SFTS virus (SFTSV), with a high fatality rate of approximately 30% in humans. In recent years, cases of contact infection with SFTSV via bodily fluids of infected dogs and cats have been reported. In this study, clinical and virological analyses were performed in two dogs in which SFTSV infection was confirmed for the first time in the Toyama prefecture. Both dogs recovered; however, one was severely ill and the other mildly ill. The amount of the SFTSV gene was reduced to almost similar levels in both dogs. In the dogs' sera, the SFTSV gene was detected at a low level but fell below the detection limit approximately 2 weeks after onset. Notably, the SFTSV gene was detected at levels several thousand times higher in urine than in other specimens from both dogs. Furthermore, the gene was detected in the urine for a long period of >2 months. The clinical signs disappeared on days 1 or 6 after onset, but infectious SFTSV was detected in the urine up to 3 weeks later. Therefore, it is necessary to be careful about contact with bodily fluids, especially urine, even after symptoms have disappeared.
Topics: Humans; Animals; Dogs; Cats; Severe Fever with Thrombocytopenia Syndrome; Cat Diseases; Bunyaviridae Infections; Dog Diseases; Phlebovirus
PubMed: 38005905
DOI: 10.3390/v15112228 -
Emerging Infectious Diseases Apr 2020We conducted an epidemiologic study of severe fever with thrombocytopenia syndrome (SFTS) in Japan during 2013-2017. Of 303 cases reported during that period, 133 (44%)...
We conducted an epidemiologic study of severe fever with thrombocytopenia syndrome (SFTS) in Japan during 2013-2017. Of 303 cases reported during that period, 133 (44%) were included in this study. The median time between onset of illness and diagnosis of SFTS shortened, from 11.5 to 3.0 days, but the case-fatality rate remained high, at 27%. In 64 patients (48%), a close contact with companion animals was reported within 2 weeks of disease onset. Of these 64 patients, 40 were surveyed further, and we confirmed that 3 had direct contact with body fluids of ill companion animals; 2 had direct contact with the saliva of an ill feral cat or pet dog. These patients reported no history of tick bite, suggesting that ill companion animals might be a source of SFTS virus transmission. Direct contact with the body fluids of ill companion animals should be avoided.
Topics: Animals; Body Fluids; Bunyaviridae Infections; Cats; Dogs; Humans; Japan; Phlebotomus Fever; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome; Tick Bites
PubMed: 32186502
DOI: 10.3201/eid2604.191011 -
Virologica Sinica Feb 2024Severe fever with thrombocytopenia syndrome (SFTS) caused by the SFTS virus (SFTSV) is an emerging disease in East Asia with a fatality rate of up to 30%. However, the...
Severe fever with thrombocytopenia syndrome (SFTS) caused by the SFTS virus (SFTSV) is an emerging disease in East Asia with a fatality rate of up to 30%. However, the viral-host interaction of SFTSV remains largely unknown. The heat-shock protein 90 (Hsp90) family consists of highly conserved chaperones that fold and remodel proteins and has a broad impact on the infection of many viruses. Here, we showed that Hsp90 is an important host factor involved in SFTSV infection. Hsp90 inhibitors significantly reduced SFTSV replication, viral protein expression, and the formation of inclusion bodies consisting of nonstructural proteins (NSs). Among viral proteins, NSs appeared to be the most reduced when Hsp90 inhibitors were used, and further analysis showed that their translation was affected. Co-immunoprecipitation of NSs with four isomers of Hsp90 showed that Hsp90 β specifically interacted with them. Knockdown of Hsp90 β expression also inhibited replication of SFTSV. These results suggest that Hsp90 β plays a critical role during SFTSV infection and could be a potential target for the development of drugs against SFTS.
Topics: Humans; Severe Fever with Thrombocytopenia Syndrome; Phlebovirus; Host Microbial Interactions; Bunyaviridae Infections
PubMed: 38008382
DOI: 10.1016/j.virs.2023.11.008 -
Journal of Virological Methods May 2023Rift Valley fever phlebovirus (RVFV) is an emerging, mosquito-borne, zoonotic pathogen. Real time RT-qPCR genotyping (GT) assays were developed to differentiate between...
Rift Valley fever phlebovirus (RVFV) is an emerging, mosquito-borne, zoonotic pathogen. Real time RT-qPCR genotyping (GT) assays were developed to differentiate between two RVFV wild-type strains (128B-15 and SA01-1322) and a vaccine strain (MP-12). The GT assay uses a one-step RT-qPCR mix, with two different RVFV strain-specific primers (either forward or reverse) with long or short G/C tags and a common primer (either forward or reverse) for each of the 3 genomic segments. The GT assay produces PCR amplicons with unique melting temperatures that are resolved in a post PCR melt curve analysis for strain identification. Furthermore, a strain specific RT-qPCR (SS-PCR) assay was developed to allow for specific detection of low titer RVFV strains in mixed RVFV samples. Our data shows that the GT assays are capable of differentiating L, M, and S segments of RVFV strains 128B-15 versus MP-12, and 128B-15 versus SA01-1322. The SS-PCR assay results revealed that it can specifically amplify and detect a low titer MP-12 strain in mixed RVFV samples. Overall, these two novel assays are useful as screening tools for determining reassortment of the segmented RVFV genome during co-infections, and could be adapted and applied for other segmented pathogens of interest.
Topics: Animals; Humans; Rift Valley Fever; Rift Valley fever virus; Genotype; Phlebovirus; Polymerase Chain Reaction
PubMed: 36801236
DOI: 10.1016/j.jviromet.2023.114693